Nowadays, skin-tanning products are commercially available for cosmetic purposes and also utilized for the clinical treatment of pigmentary disorders such as vitiligo. Vitiligo is acquired pigment disorder that is caused by melanocyte malfunction and depigmentation.
Melanogenesis is a physiological process in response to UV exposure. There are more than 100 distinct genes directly or indirectly involved in the regulation of melanogenesis. In mammals, melanogenesis is directly regulated by three enzymes, tyrosinase (TYR), tyrosinase related protein-1 (TRP-1) and tyrosinase related protein-2 (TRP-2). Tyrosinase is regarded as the rate-limiting enzyme of melanogenesis. It plays a pivotal role in the modulation of melanin production by catalyzing the hydroxylation of tyrosine into dihydroxyphenylalanine (DOPA) and the further oxidation of DOPA into DOPAquinone by tyrosinase. TRP-2, which functions as a DOPAchrome tautomerase, catalyzes the rearrangement of DOPAchrome to 5,6-dihydroxyl indole-2-carboxylic acid (DHICA), whereas TRP-1 oxidizes DHICA to a carboxylated indole-quinone. Microphthalmia-associated transcription factor (MITF) is known to be the master regulator of melanocyte differentiation, pigmentation, proliferation and survival. It is a major transcriptional regulator of the tyrosinase family genes TYR, TRP-1 and TRP-2 responsible for pigmentation.
Protein kinase A (PKA) signaling has been implicated in melanogenesis. PKA can be activated by the elevation of cellular cAMP, and PKA activation can in turn lead to the activation of MITF transcriptional activity through the activation of CREB, resulting in the expression of tyrosinase, TRP-1, and TRP-2 genes. On the other hand, Wnt/β-catenin signaling has also been involved in the melanogenesis based on the finding that β-catenin formed a complex with lymphocyte enhancer factor-1 (LEF-1) to up-regulate expression of the MITF gene. Study also showed that β-catenin directly interacts with the MITF protein itself, then activates MITF-specific target genes.
Gynostemma pentaphyllum (Gp) is a perennial creeping herb in the family of Cucurbitaceae. It is widely distributed in China, particularly in the southern region of the Qinling Mountains and the Yangtze River. The earliest documented use of Gp as a vegetable was found in the manuscript titled ‘Herbs for Famine’ which was published in the Ming Dynasty (1368-1644 A.D.) The ‘Compendium of Materia Medica’, a monumental work in the Chinese medicine field by Li Shi-Zhen, stated that Gp can be used for lowering cholesterol levels, regulating blood pressure, strengthening gastritis, as well as reducing inflammation. Many studies showed that Gp may possess anti-oxidant, anti-apoptotic and anti-carcinogenic properties in vitro and animal studies. Lin C C, Huang P C, Lin J M. Antioxidant and hepatoprotective effects of Anoectochilus formosanus and Gynostemma pentaphyllum. Am. J. Chinese Med. 2000, 28:87-96 demonstrated that Gp exerts an antioxidant effect and hepatoprotective activity on acetaminophen-induced liver injury in rats; Zhou Z T, Wang Y, Zhou Y M, Zhang S L. Effect of Gynostemma pentaphyllum Mak on carcinomatous conversions of golden hamster cheek pouches induced by dimethylbenzanthracene: a histological study. Chinese Med. J. Peking 1998, 111:847-850 demonstrated that Gp could inhibit and reverse the carcinomatous conversions of leukoplasia of golden hamster cheek pouches induced by dimethylbenzanthracene, indicating its positive anti-carcinogenic activities; Chen J C, Chung J G, Chen L D. Gypenoside induces apoptosis in human Hep3B and HA22T tumor cells. Cytobios 1999, 100:37-48 demonstrated that Gp inhibited cell viability through induction of apoptosis in human Hep3B and HA22T tumor cells; Ma Z R and Yang Z B. Scavenging effects of Astragalus and Gynostemma pentaphyllum with its product on O2 and OH. Zhong Yao Cai 1999, 22:303-6 demonstrated that Gp could scavenge the active oxygen free radicals effectively and Ginsenoside Rb1 extracted from Gp showed a strong effect on scavenging the .OH; and Wang Q F, Chen J C, Hsieh S J, Cheng C C, Hsu S L. Regulation of Bcl-2 family molecules and activation of caspase cascade involved in gypenosides-induced apoptosis in human hepatoma cells. Cancer Lett. 2002, 183:169-78 demonstrated that Gp could induce apoptosis through the up-regulation of Bax and Bak, and down-regulation of Bcl-2, release of mitochondrial cytochrome c and activation of a caspase cascade in human hepatoma Huh-7, Hep3B and HA22T cell lines. Also, it is previously demonstrated in Tai W C S, Zhang S Z H, Jiang Z H, Hsiao W W L. Isolation of Active ingredients with anticancer activity of total triterpenoids saponins of Gymnostemma Pentaphyllum by cell-based co-culture activity-guided fractionation assay, 2010, the 9th CGCM meeting that GpS can kill GFP/Ras transformed cancer cells in the presence of normal cells in the co-culture assay system, which showed the anti-cancer effect of GpS.
Gp contains over a hundred different triterpenoid saponins that structurally resemble ginseng saponins. Specifically, gypenoside 3 is identical to ginsenoside Rb1, gypenoside 4 is identical to ginsenoside Rb3, gypenoside 8 is identical to ginsenoside Rd, and gypenoside 12 is identical to ginsenoside F2. Many of the other gypenosides are closely related structurally to the ginsenosides and include the 6′-malonyl derivatives characteristic of ginseng. Other constituents reported from Gp include sterols with the ergostane, sholestane, and stigmastane skeletons, and also, the flavonoid glycosides ombuin and ombuoside, rutin, yixingensin, polysaccharides, vitamins, minerals, carotenoids and amino acids.
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